Food and water intake in WT (+/+) mice and SGLT5-deficient mice (−/−). Daily intake of

<p>(<b>A</b>) <b>food and</b> (<b>B</b>) <b>water of mice at 17 weeks of age.</b> (C) Calculated daily energy intake. Data are presented as means ± S.E.M (n = 8–10). ### P<0.001 versus respective plain water control.</p

Generation of SGLT5-deficient mice and their fructose and mannose uptake by renal BBMV s.

<p>(A) Schematic representation of the strategy for targeting the <i>Slc5a10</i> gene. A targeting vector was constructed by inserting a neomycin resistant (<i>neo</i>) gene cassette to disrupt exons 3–6 of the <i>Slc5a10</i> genomic locus on a BAC genomic clone. Arrows indicate PCR primers for genotyping. (B) A representative result of genotyping the offspring obtained by intercrossing heterozygous-deficient mice. Wild type and null alleles are detected as signals of 900 bp and 350 bp, respectively. <i>Wt</i>: Wild type mice, <i>He</i>: Heterozygous null mutant, <i>Ho</i>: Homozygous null mutant. (C) Sodium-dependent uptake of fructose and (D) mannose in BBMVs of WT mice (+/+) and SGLT5-deficient mice (−/−). (E) Sodium-independent uptake of fructose and (F) mannose in BBMVs of WT mice (+/+) and SGLT5-deficient mice (−/−). Data are presented as means ± S.D. Data are derived from 3 independent experiments.</p

SGLT5 distribution and fructose uptake.

<p>(A) Tissue distribution of mouse SGLT5 and (B) SGLT5-mediated fructose uptake in COS-7 cells. Data are presented as means ± S.D. Data are derived from 3 independent experiments.</p

Gene expression analysis. Quantitative RT-PCR was performed with total RNA isolated from (A) the liver and (B) the kidney of WT mice (+/+) and SGLT5-deficient mice (−/−) given plain water or high fructose (HF) water.

<p><i>MAPK1</i> was used as an internal control. Data are presented as means ± S.E.M. <i>n</i> = 3 (A). <i>n</i> = 8–10 (B).</p

Oral glucose tolerance test with WT mice (+/+) and SGLT5-deficient mice (−/−) given plain water or fructose water (HF).

<p>Fasted 21-week-old male mice received an oral dose of glucose (2 g/kg). Plasma glucose levels were determined at the indicated time points. Data are presented as means ± S.E.M (<i>n</i> = 8–10). ### <i>P</i><0.001 versus respective water controls by analysis of covariance (ANCOVA).</p

Influence of the long-term consumption of fructose on tissue weight and lipid metabolism.

<p>(A) Plasma triglyceride levels of WT mice (+/+) and SGLT5-deficient mice (−/−). (B) Plasma total cholesterol levels. (C) Weight of epididymal fat. (D) Weight of the liver. (E) Hepatic triglyceride levels. (F) Histopathological analysis of the liver sections. Two sections per mouse were stained with Sudan III. Representative images are shown (scale bar, 50 µm). Data are presented as means ± S.E.M (<i>n</i> = 8–10). * <i>P</i><0.05, *** <i>P</i><0.001 versus WT mice given 30% fructose water. # <i>P</i><0.05, ## <i>P</i><0.01, ### <i>P</i><0.001 versus respective plain water controls.</p

Effect of high fructose consumption in WT mice and SGLT5-deficient mice.

<p>(A) Plasma glucose levels of WT mice (+/+) and SGLT5-deficient mice (−/−) were measured every 2 weeks. <i>HF</i>: Mice given water containing high fructose. (B) Growth curves of WT mice and SGLT5-deficient mice. (C) Plasma samples were collected after 6 h fasting at 21 weeks of age, and immunoreactive insulin (<i>IRI</i>) was determined. (D) Plasma fructose concentrations measured in plasma samples collected under anesthesia after 3 h fasting. <i>Open circles</i> represent individual data. (E and F) WT mice and SGLT5-deficient mice given plain water or fructose water were maintained in metabolic cages and 24-h urine samples were collected. Urinary fructose excretion was calculated by multiplying urinary fructose concentration by the amount of urine. Data are presented as means ± S.E.M (<i>n</i> = 8–10). *** <i>P</i><0.001 versus WT mice given 30% fructose water. # <i>P</i><0.05, ## <i>P</i><0.01, ### <i>P</i><0.001 versus respective plain water controls. +++ <i>P</i><0.001 versus WT mice given plain water.</p

Dual Involvement of Growth Arrest-Specific Gene 6 in the Early Phase of Human IgA Nephropathy

<div><p>Background</p><p>Gas6 is a growth factor that causes proliferation of mesangial cells in the development of glomerulonephritis. Gas6 can bind to three kinds of receptors; Axl, Dtk, and Mer. However, their expression and functions are not entirely clear in the different glomerular cell types. Meanwhile, representative cell cycle regulatory protein p27 has been reported to be expressed in podocytes in normal glomeruli with decreased expression in proliferating glomeruli, which inversely correlated with mesangial proliferation in human IgA nephropathy (IgAN).</p><p>Methods</p><p>The aim of this study is to clarify Gas6 involvement in the progression of IgAN. Expression of Gas6/Axl/Dtk was examined in 31 biopsy proven IgAN cases. We compared the expression levels with histological severity or clinical data. Moreover, we investigated the expression of Gas6 and its receptors in cultured podocytes.</p><p>Results</p><p>In 28 of 31 cases, Gas6 was upregulated mainly in podocytes. In the other 3 cases, Gas6 expression was induced in endothelial and mesangial cells, which was similar to animal nephritis models. Among 28 podocyte type cases, the expression level of Gas6 correlated with the mesangial hypercellularity score of IgAN Oxford classification and urine protein excretion. It also inversely correlated with p27 expression in glomeruli. As for the receptors, Axl was mainly expressed in endothelial and mesangial cells, while Dtk was expressed in podocytes. In vitro, Dtk was expressed in cultured murine podocytes, and the expression of p27 was decreased by Gas6 stimulation.</p><p>Conclusions</p><p>Gas6 was uniquely upregulated in either endothelial/mesangial cells or podocytes in IgAN. The expression pattern can be used as a marker to classify IgAN. Gas6 has a possibility to be involved in not only mesangial proliferation via Axl, but also podocyte injury via Dtk in IgAN.</p></div

Demographic, clinical parameters and pathological findings.

<p>IgA epi, IgA epithelial type. IgA e/m, IgA endothelial and mesangial type.</p><p>M score, Mesangial hyprecellularity score. S score, Segmantal glomeruloscrelosis score. E score, Endocapillary hypercellularity score.</p><p>T score, Tubular atrophy/interstitial fibrosis score.</p

MOESM2 of Selective pharmacological inhibition of DDR1 prevents experimentally-induced glomerulonephritis in prevention and therapeutic regime

Additional file 2. Additional tables